The objective is to understand how proteins recognize specific sequences of double stranded DNA and to understand how the activities of gene regulatory proteins are controlled by interactions with other proteins. Genetic, biochemical, and structural studies will be used to elucidate the detailed mechanism by which the Arc and Mnt repressors of bacteriophage P22 bind to their respective operator sequences, and to characterize mutations that enhance or alter the binding specificity of the lambda repressor and lambda Cro proteins. Mutations that abolish or enhance cooperative interactions between lambda repressor molecules bound at adjacent operator sites will also be isolated, and the effects of these mutations on protein-mediated DNA looping and the linear polymerization of repressor in solution will be determined. Finally, the mechanisms of RecA-mediated and P22 antirepressor-mediated inactivation of lambda repressor will be explored by studying the biochemical properties of mutant proteins that display altered properties in the inactivation reactions.